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The retention of patients under methadone maintenance treatment (MMT) is an indication for the effectiveness of the therapy. We aimed to explore the relation between mortality and the cumulative MMT duration.
Methods
A retrospective cohort analysis was performed using Taiwan Illicit Drug Issue Database (TIDID) and National Health Insurance Research Database (NHIRD) during 2012–2016. We included 9149 and 11 112 MMT patients as the short and long groups according to the length of their cumulative MMT duration, 1–364 and ⩾365 days, respectively. The risk of mortality was calculated by Cox proportional hazards regression model with time-dependent exposure to MMT, and the survival probability was plotted with the Kaplan-Meier curve.
Results
The mortality rates were 2.51 and 1.51 per 100 person-years in the short and long cumulative MMT duration groups, respectively. After adjusting for on or off MMT, age, sex, marital status, education level, maximum methadone dose, and comorbidities (human immunodeficiency virus, depression, hepatitis C virus, hepatitis B virus, alcoholic liver disease, and cardiovascular disease), the long group had a lower risk of death (hazard ratio = 0.67; 95% confidence interval 0.60–0.75) than the short group. Increased risk was observed in patients with advanced age, being male, unmarried, infected by HIV, HCV, and HBV, and diagnosed with depression, ALD, and CVD. Causes of death were frequently related to drug and injury.
Conclusions
Longer cumulative MMT duration is associated with lower all-cause and drug-related mortality rate.
Sustaining adequate nutritional needs of a population is a challenging task in normal times and a priority in times of crisis. There is no ‘one-size-fits-all’ solution that addresses nutrition. In relevance to the COVID-19 (coronavirus disease 2019) pandemic crisis, viral infections in general and RNA viruses in particular are known to induce and promote oxidative stress, consequently increasing the body’s demand for micronutrients, especially those related to antioxidant enzymic systems, thus draining the body of micronutrients, and so hindering the human body’s ability to cope optimally with oxidative stress. Common polymorphisms in major antioxidant enzymes, with world population minor allele frequencies ranging from 0·5 to 50 %, are related to altered enzymic function, with substantial potential effects on the body’s ability to cope with viral infection-induced oxidative stress. In this review we highlight common SNP of the major antioxidant enzymes relevant to nutritional components in the context of viral infections, namely: superoxide dismutases, glutathione peroxidases and catalase. We delineate functional polymorphisms in several human antioxidant enzymes that require, especially during a viral crisis, adequate and potentially additional nutritional support to cope with the pathological consequences of disease. Thus, in face of the COVID-19 pandemic, nutrition should be tightly monitored and possibly supplemented, with special attention to those carrying common polymorphisms in antioxidant enzymes.
Primary liver cancer is the third leading cause of cancer-related death worldwide. Most patients are diagnosed at late stages with poor prognosis; thus, identification of modifiable risk factors for primary prevention of liver cancer is urgently needed. The well-established risk factors of liver cancer include chronic infection with hepatitis B virus (HBV) or hepatitis C virus (HCV), heavy alcohol consumption, metabolic diseases such as obesity and diabetes, and aflatoxin exposure. However, a large proportion of cancer cases worldwide cannot be explained by current known risk factors. Dietary factors have been suspected as important, but dietary aetiology of liver cancer remains poorly understood. In this review, we summarised and evaluated the observational studies of diet including single nutrients, food and food groups, as well as dietary patterns with the risk of developing liver cancer. Although there are large knowledge gaps between diet and liver cancer risk, current epidemiological evidence supports an important role of diet in liver cancer development. For example, exposure to aflatoxin, heavy alcohol drinking and possibly dairy product (not including yogurt) intake increase, while intake of coffee, fish and tea, light-to-moderate alcohol drinking and several healthy dietary patterns (e.g. Alternative Healthy Eating Index) may decrease liver cancer risk. Future studies with large sample size and accurate diet measurement are warranted and need to consider issues such as the possible aetiological heterogeneity between liver cancer subtypes, the influence of chronic HBV or HCV infection, the high-risk populations (e.g. cirrhosis) and a potential interplay with host gut microbiota or genetic variations.
Hepatitis C virus (HCV) represents a major public health problem, while the identification of a HCV genotype is clinically very important for therapy prescription. The aim of the present study was to determine the HCV genotype distribution patients from northern Greece with HCV RNA positive viral load and to identify whether there is a shift in this distribution, during 2009–2017. The study was performed on 915 HCV positive patients and according to the results, genotype 3 was the most prevalent genotype (Ν = 395, 43.2%) followed by genotype 1 (Ν = 361, 39.5%). Regarding the gender of the patients, genotype 1 was mostly detected in women. Moreover, genotype 1 was associated with higher viral loads, while genotype 3 was most frequently detected in patients with a history of intravenous drug use. In conclusion, our results show that genotype 3 is the most prevalent genotype in Greece during the last decade as opposed to older epidemiological studies, likely due to intravenous drug use becoming the major source of infection.
Seroprevalence estimation using cross-sectional serosurveys can be challenging due to inadequate or unknown biological cut-off limits of detection. In recent years, diagnostic assay cut-offs, fixed assay cut-offs and more flexible approaches as mixture modelling have been proposed to classify biological quantitative measurements into a positive or negative status. Our objective was to estimate the prevalence of anti-HCV antibodies among drug users (DU) in France in 2011 using a biological test performed on dried blood spots (DBS) collected during a cross-sectional serosurvey. However, in 2011, we did not have a cut-off value for DBS. We could not use the values for serum or plasma, knowing that the DBS value was not necessarily the same. Accordingly, we used a method which consisted of applying a two-component mixture model with age-dependent mixing proportions using penalised splines. The component densities were assumed to be log-normally distributed and were estimated in a Bayesian framework. Anti-HCV prevalence among DU was estimated at 43.3% in France and increased with age. Our method allowed us to provide estimates of age-dependent prevalence using DBS without having a specified biological cut-off value.
Chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are usually asymptomatic for decades, thus targeted screening can prevent liver disease by timely diagnosis and linkage to care. More robust estimates of chronic HBV and HCV infections in the general population and risk groups are needed. Using a modified workbook method, the total number of ever chronically infected individuals in the Netherlands in 2016 was determined using population size and prevalence estimates from studies in the general and high-risk population. The estimated 2016 chronic HBV infection prevalence is 0.34% (low 0.22%, high 0.47%), corresponding to approximately 49 000 (low 31 000, high 66 000) HBV-infected individuals aged 15 years and older. The estimated ever-chronic HCV infection prevalence is 0.16% (low 0.06%, high 0.27%), corresponding to approximately 23 000 (low 8000, high 38 000) ever-chronic HCV-infected individuals. The prevalence of chronic HBV and HCV infections in the Netherlands is low. First-generation migrants account for most infections with 81% and 60% of chronic HBV and HCV infections, respectively. However, about one-fifth of HCV infections is found in the general population at low risk. This method can serve as an example for countries in need of more accurate prevalence estimates, to help the design and evaluation of prevention and control policies.
The probability of a Black African finding a matched unrelated donor for a hematopoietic stem cell transplant is minimal due to the high degree of genetic diversity amongst individuals of African origin. This problem could be resolved in part by the establishment of a public cord blood (CB) stem cell bank. The high prevalence of human immunodeficiency virus (HIV) amongst women attending antenatal clinics in sub-Saharan Africa together with the risk of mother-to-child transmission increases the risk of transplant transmissible infection. In addition to screening the mother in a period inclusive of 7 days prior to the following delivery, we propose that all CB units considered for storage undergo rigorous and reliable screening for HIV. The Ultrio-plus® assay is a highly specific and sensitive test for detecting HIV, hepatitis-B and hepatitis-C viruses in peripheral blood. We validated the Ultrio-plus® assay for analytical sensitivity in detecting HIV in CB at the level of detection of the assay. Until more comprehensive and sensitive methods are developed, the sensitivity and reliability of the Ultrio-plus® assay suggest that it could be used for the routine screening of CB units in conjunction with currently recommended maternal screening to reduce the risk of transplant transmissible infection.
Introduction: Hepatitis C virus (HCV) infection represents a significant public health problem in Canada and it is estimated that nearly half of individuals with chronic hepatitis C infection are unaware of their disease status. Previous studies of urban emergency department (ED) based screening programs have shown a prevalence ranging from 7.3 to 26% in high risk patients presenting to the ED . The advent of new treatment regimens with high rates of virologic cure strengthens the case for identifying the optimal setting for screening and testing individuals who may benefit from treatment. The proposed pilot project of ED-based screening for hepatitis C virus will aim to determine the prevalence of undiagnosed HCV infection and to link patients with chronic HCV infection to appropriate specialized follow-up care. Methods: We will be conducting a prospective cohort study of patients presenting to an urban emergency department between March and May 2018. Patients will be screened using high risk criteria for HCV infection as per national guidelines. Eligible patients will be offered and consented for a rapid point of care antibody test. Individuals with a positive antibody screen will have confirmatory testing and be linked to hepatology follow-up. The primary outcome will be the prevalence of hepatitis C virus among tested patients. Secondary outcomes will include the proportion of high risk patients without a primary care MD or access to alternate care settings where screening may occur, as well as the proportion of HCV-positive patients who are successfully linked to care. Results: We expect to screen approximately 2000 participants during the study period leading to an estimated 400 rapid antibody tests. Based on published results from other centres, we estimate that a significant proportion of screened patients will test positive for chronic HCV infection ( > 10%). Descriptive analyses will be performed for all variables using proportions with 95% confidence intervals. Conclusion: To our knowledge, no emergency department in Canada has undertaken protocoled HCV screening using rapid antibody testing in the ED. Results will inform the future development of integrated ED-based screening programs in novel settings more likely to be accessed by the at-risk population. Linking patients with chronic HCV infection to appropriate care will decrease the number of individuals developing HCV-related cirrhosis and hepatocellular carcinoma, thereby improving patient outcomes and reducing the future impact on our health care system.
To understand increasing rates of hepatitis C virus (HCV) infection in Tennessee, we conducted testing, risk factor analysis and a nested case–control study among persons who use drugs. During June–October 2016, HCV testing with risk factor assessment was conducted in sexually transmitted disease clinics, family planning clinics and an addiction treatment facility in eastern Tennessee; data were analysed by using multivariable logistic regression. A nested case–control study was conducted to assess drug-using risks and behaviours among persons who reported intranasal or injection drug use (IDU). Of 4753 persons tested, 397 (8.4%) were HCV-antibody positive. HCV infection was significantly associated with a history of both intranasal and IDU (adjusted odds ratio (aOR) 35.4, 95% confidence interval (CI) 24.1–51.9), IDU alone (aOR 52.7, CI 25.3–109.9), intranasal drug use alone (aOR 2.6, CI 1.8–3.9) and incarceration (aOR 2.7, CI 2.0–3.8). By 4 October 2016, 574 persons with a reported history of drug use; 63 (11%) were interviewed further. Of 31 persons who used both intranasal and injection drugs, 26 (84%) reported previous intranasal drug use, occurring 1–18 years (median 5.5 years) before their first IDU. Our findings provide evidence that reported IDU, intranasal drug use and incarceration are independent indicators of risk for past or present HCV infection in the study population.
Hepatitis C virus (HCV) infection is one of the leading causes of death and morbidity associated with liver disease. Risk factors identified for the transmission of HCV include contaminated blood products, intravenous drug use, body piercing, an infected mother at birth, sexual activity, and dental therapy, among others. However, the exact diversity of the HCV genotype and genetic variation among patients with low-risk factors is still unknown. In this study, we briefly described and analysed the genotype distribution and genetic variation of HCV infections with low-risk factors using molecular biology techniques. The results suggested that genotype 1b was predominant, followed by genotypes 2a and 1a. Genetic variations in the 5′ UTR sequences of HCV were identified, including point mutations, deletions, and insertions. The frequency of genetic variations in 1b was higher than in 2a. This study provides considerable value for the prevention and treatment of liver disease caused by HCV among patients with low-risk factors and for the development of HCV diagnostic reagents and vaccines.
Hepatitis C virus (HCV) infection is a public health issue worldwide. Injecting drug use remains the major mode of transmission in developed countries. Monitoring the HCV transmission dynamic over time is crucial, especially to assess the effect of harm reduction measures in drug users (DU). Our objective was to estimate the prevalence and incidence of HCV infection in DU in France using data from a repeated cross-sectional survey conducted in 2004 and 2011. Age- and time-dependent HCV prevalence was estimated through logistic regression models adjusted for HIV serostatus or injecting practices. HCV incidence was estimated from a mathematical model linking prevalence and incidence. HCV prevalence decreased from 58·2% [95% confidence interval (CI) 49·7–66·8] in 2004 to 43·2% (95% CI 38·8–47·7) in 2011. HCV incidence decreased from 7·9/100 person-years (95% CI 6·4–9·4) in 2004 to 4·4/100 person-years (95% CI 3·3–5·9) in 2011. HCV prevalence and incidence were significantly associated with age, calendar time, HIV serostatus and injecting practices. In 2011, the highest estimated incidence was in active injecting DU (11·2/100 person-years). Given the forthcoming objective of generalizing access to new direct antiviral agents for HCV infection, our results contribute to decision-making and policy development regarding treatment scale-up and disease prevention in the DU population.
Hepatitis C virus (HCV) has become a global public health problem. Many studies have been conducted to identify risk factors for HCV infection. However, some of these studies reported inconsistent results. Using data collected from 11 methadone clinics, we fit both a non-spatial logistical regression and a geographically weighted logistic regression to analyse the association between HCV infection and some factors at the individual level. This study enrolled 5401 patients with 30·0% HCV infection prevalence. The non-spatial logistical regression found that injection history, drug rehabilitation history and senior high-school education or above were related to HCV infection; and being married was negatively associated with HCV infection. Using the spatial model, we found that Yi ethnicity was negatively related to HCV infection in 62·0% of townships, and being married was negatively associated with HCV infection in 81·0% of townships. Senior high-school education or above was positively associated with HCV infection in 55·2% of townships of the Yi Autonomous Prefecture. The spatial model offers better understanding of the geographical variations of the risk factors associated with HCV infection. The geographical variations may be useful for customizing intervention strategies for local regions for more efficient allocation of limited resources to control transmission of HCV.
Dietary cholesterol induces hepatic inflammation and fibrosis in animals. We aimed to determine whether dietary cholesterol affects liver-related mortality in hepatitis C virus (HCV)-infected patients. We performed a retrospective cohort study using extended follow-up data from the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis Trial. The study included HCV patients with advanced fibrosis and compensated cirrhosis. The analysis included 657 patients who completed two FFQ. We assessed whether cholesterol intake, measured in mg/4184 kJ (mg/1000 kcal) of energy intake, was associated with liver-related death or transplantation. In 4·7 (sd 1·6) years, the incidence of liver-related death (n 46) or transplantation (n 52) was 31·8/1000 person-years. The relationship between cholesterol intake and liver-related death or transplantation was significantly different between men and women (test for interaction, P value=0·01). Each higher quartile of cholesterol intake was associated with an increased risk for liver-related death or transplantation in women (adjusted hazard ratio (AHR) 1·83; 95 % CI 1·12, 2·99; Ptrend=0·02), but not in men (AHR 0·96; 95 % CI 0·76, 1·22; Ptrend=0·73). Compared with women whose cholesterol intake was within the recommended guidelines (300 mg/d with a 8368 kJ (2000 kcal) diet), women who consumed more cholesterol had significantly increased risk for liver-related death or transplantation (AHR 4·04; 95 % CI 1·42, 11·5). High dietary cholesterol was associated with an increased risk for liver-related death and transplantation in HCV-infected women with advanced fibrosis or compensated cirrhosis. Future studies should assess whether reducing cholesterol intake, among women who consume an excessive amount, can decrease HCV-related mortality.
This study aimed to estimate the prevalence and risk factors for hepatitis C virus (HCV) infection in Mexican Americans living in South Texas. We tested plasma for the presence of HCV antibody from the Cameron County Hispanic Cohort (CCHC), a randomized, population-based cohort in an economically disadvantaged Mexican American community on the United States/Mexico border with high rates of chronic disease. A weighted prevalence of HCV antibody of 2·3% [n = 1131, 95% confidence interval (CI) 1·2–3·4] was found. Participants with diabetes had low rates of HCV antibody (0·4%, 95% CI 0·0–0·9) and logistic regression revealed a statistically significant negative association between HCV and diabetes (OR 0·20, 95% CI 0·05–0·77) after adjusting for sociodemographic and clinical factors. This conflicts with reported positive associations of diabetes and HCV infection. No classic risk factors were identified, but important differences between genders emerged in analysis. This population-based study of HCV in Mexican Americans suggests that national studies do not adequately describe the epidemiology of HCV in this border community and that unique risk factors may be involved.
Hepatitis C virus (HCV) infection is common among intravenous drug users, and because of the long latent period, HCV liver disease is set to increase.
Objectives:
We sought to examine practice guidelines regarding treatment of HCV in drug users and to review the evidence for current practices.
Methods:
A structured search of the Pubmed database, websites of the National Institute for Clinical Excellence and national and international expert groups and opinion of independent experts in the field.
Results and Conclusions:
All those infected with HCV need to be assessed to ascertain whether they have active ongoing viral replication and the extent of liver damage. HCV-infected individuals should be educated about the modes of transmission and means of reducing the risk of infecting others. They should also be advised to avoid cofactors (especially alcohol) that accelerate the progression of liver disease. Specific treatment with antivirals can cause viral clearance and prevent the progression of liver disease. Therapy is effective in those on opiate-replacement treatments and also in motivated individuals who continue to use intravenous drugs. The decision whether to treat drug users should be made jointly by specialists in the management of viral hepatitis and addiction on a case-by-case basis. Current combination drug regimens are expensive but are claimed to be cost-effective, and are certainly much less costly than managing end-stage liver disease. In addition to satisfactory sustained viral response rates, other benefits such as a beneficial effect on drug habit, self-esteem and rehabilitation have been reported. Encouraging suitable drug users to take-up and comply with treatment seems to be more easily achieved in supportive drug dependency unit settings (rather than the more formal surroundings of a hospital clinic).
We conducted a case-control study involving 150 genotype 3 chronic hepatitis C virus (HCV) patients and 150 healthy controls to investigate the association of polymorphisms in the interleukin-10 (IL-10) gene with chronic HCV infection and the association of these polymorphic variants with the combination of pegylated interferon (Peg-IFN) and ribavirin therapy response. Our data revealed that the GG genotype of IL-10 –1082A/G exhibited significant association with genotype 3 chronic HCV infection compared to controls. Treatment response data also showed a significant increase in risk for the GG genotype of IL-10 –1082A/G in response-relapse patients or non-responder patients compared to sustained virological response patients. Further, a significant increase in risk was also revealed for the CC genotype of IL-10 –592A/C in response-relapse patients or non-responder patients compared to sustained virological response patients, suggesting a role of the GG genotype of IL-10 –1082A/G and CC genotype of IL-10 –592A/C in the treatment outcome of combined Peg-IFN/ribavirin therapy.
Genotypes are associated with the natural course of hepatitis C virus (HCV) infection and response to antiviral therapy for HCV. HCV genotype 1b has been the dominant genotype in Japan, where the prevention of HCV transmission through blood transfusion or nosocomial infection has been established since 1990. The distribution of HCV genotype was investigated based on patient's birth year in 5515 HCV-infected Japanese individuals at three institutions from different areas of Japan. At all three institutions, the proportion of HCV genotype 1b decreased and was <50% in individuals born after 1970. By contrast, the percentage of HCV genotype 2b increased in subsequent birth cohorts after 1920–1929. Significant changes in HCV genotype distribution were observed across Japan regardless of area.
We studied hepatitis C virus (HCV) prevalence and risk factors for HCV infection in a sample of Brazilian HIV-positive patients. A cross-sectional study was conducted with 580 HIV-positive patients from a specialized HIV/AIDS diagnosis and treatment centre in southern Brazil. All patients were interviewed for socio-demographic and risk factors and tested for HCV antibodies and HCV-RNA detection. A multivariate analysis was performed to identify risk factors for HCV infection. A total of 138 (24%) patients had past or chronic hepatitis C. The following risk factors were associated with HCV infection for each gender: alcohol misuse and injecting drug use in women (P < 0·001) and low educational level, smoking drug use, and injecting drug use in men (P < 0·01). These results suggest that alcohol misuse, low educational level, smoking drug use, and injecting drug use are probable risk factors for HCV infection in HIV-positive patients. This information contributes to an understanding of the epidemiology of HIV/HCV co-infection in Brazil.
Viruses are obligate intracellular parasites that rely on the host cell for expansion.With the development of global analyses techniques like transcriptomics, proteomics andsiRNA library screening of complete cellular gene sets, a large range of host cell factorshave been discovered that either support or restrict virus growth. Here we summarize someof the recent findings and focus our discussion on the hepatitis C virus and the humanimmunodeficiency virus, two major pathogens that threat global health. The identificationof cellular proteins affecting multiple viruses points to the existence of centralregulation nodes that might be exploited for both, a quantitative description ofhost-virus interactions within single infected cells and the development of novel,broad-spectrum antiviral drugs.
To evaluate the prevalence of hepatitis C virus (HCV) and/or hepatitis B virus (HBV) infections in HIV-infected patients in China, an epidemiological serosurvey was conducted from May 2007 to September 2008 using a random cluster sampling design of infectious disease hospitals in seven high HIV-prevalent provinces (municipalities). Univariate analysis and logistic regression were used to study the determinants of HIV and HBV and/or HCV co-infection. The overall prevalence was 41·83% (95% CI 40·36–43·30) for anti-HCV and 12·49% (95% CI 11·50–13·48) for HBsAg, respectively. The prevalence of anti-HCV and HBsAg varied according to the route of HIV transmission. Compared to those with sexually acquired HIV infection, intravenous drug users and blood donors/recipients had the greatest risk of carrying anti-HCV. Needle sharing and unprotected sexual exposures are important modes of transmission for HBV. Further interventions including health education and harm reduction strategies should be implemented in high-risk populations.